The proposed Mentored Patient-Oriented Research Career Development Award outlines a program of career development and research in clinical pediatric psychopharmacology. A focus of this program will be a clinical trial with methylphenidate in 160 children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Although stimulant medications are regarded as first-line treatments for ADHD, individual children show tremendous differences in response to drug, and there is no method to determine a priori the particular stimulant or dose likely to provide optimal benefit. The Specific Aims of the study will address possible underlying mechanisms for this variability in response to stimulant treatment. Implications of this award may be enhanced understanding of factors contributing to individual differences in response to medication and optimization of pharmacological response to ADHD and other psychiatric disorders. The candidate is an accomplished clinician and educator. The educational and research plan is designed to facilitate a change in career emphasis from clinician and clinical teacher to clinical investigator. The proposed research is specifically intended to provide mentored research experience in the application of emerging concepts from basic sciences to clinical investigations in child mental health. The five-year career development plan includes didactic instruction in neurosciences and clinical research at the UCLA Neuropsychiatric Institute and biomathematics at the UCLA School of Medicine. The proposed educational plan includes courses in clinical research methodologies, pharmacokinetics, neurophysiology, statistical analysis, neurochemistry, neuropharmacology, and human genetics. Additional time will be devoted to supervised individual courses of study in molecular psychiatry, laboratory methods, clinical pharmacology, and medical research ethics. In addition to funding the candidate's transition to independent research the proposed study would also contribute to our knowledge of the basis of individual response to medication in psychiatric disorders.